What we investigate and why
Our research is aimed at understanding how maternal milk affects immune development, education and long term homeostasis. A major objective guiding our work is the identification of factors that could endow breastfeeding with the capacity to prevent allergic and metabolic disease as potently as it does for infectious disease. Our research uses animal model and human samples from birth cohorts to perform a translational research combining the team longstanding expertise in neonate immunology and the School excellence in biochemistry.
Identification of protective and risk factors that are specific to early life period for allergic disease prevention
We propose that maternal milk composition has not adapted to the needs of allergy prevention due to the recent and rapid increase of allergy. Breast milk contains bioactive compounds known to impact on critical factors for allergy development: gut barrier function, microbiota metabolites production and oral tolerance induction. Modulation of breast milk composition towards a composition favouring immune tolerance may be the best strategy to counteract allergy development.
We have shown both in animal models and in human birth cohorts that the presence of tiny amounts of allergen in breast milk can have long-term impact on allergic disease susceptibility. Some allergens in breast milk such as egg could prevent allergy (Verhasselt, Milcent et al. 2008, Mosconi, Rekima et al. 2010, Turfkruyer, Rekima et al. 2016) while others such as from house dust mite (HDM) increase the risk of developing allergy (Macchiaverni, Rekima et al. 2014, Baiz, Macchiaverni et al. 2017). Recently, we have identified that HDM protease are essential for priming neonate gut immune system.
In this project, we will go further into the identification of the molecular characteristics of HDM protease that make them so special to induce allergy priming through the gut. We will also search for the presence of HDM protease inhibitors in maternal milk since modulating the function and/or levels of such inhibitors may be a promising strategy to prevent allergies by breastfeeding. The realization of the project will involve molecular biology tools to generate HDM allergens with mutated proteolytic activities and various biochemical techniques to measure protease inhibitors in human breast milk.
Impact of colostrum on early post-natal and adult metabolic and immune homeostasis
Colostrum is produced during the first 2 -3 days by the mammary gland and profoundly differs both qualitatively and quantitatively from mature breast milk indicating the necessity to address specifically its potential health impact. A recent large scale study (Group 2016) in developing countries showed a major impact of early initiation of breastfeeding on the prevention of neonatal mortality and morbidity up to 6 months of age (up to 40% decrease). Currently, there is no data on the specific impact of colostrum on major public health issues such as diabetes and allergy. Importantly, there is a worldwide lack of maternal colostrum administration.
Our team is determining (1) the physiological impact of colostrum on the early development of the gut microbiota, immune regulation, metabolic homeostasis, and their crosstalk in early life (2) the impact of colostrum intake, and its lack, on obesity and allergic disease risk in adulthood and (3) the dietary factors and physiological actors in early life which condition long term health in order to establish a sustainable prevention of obesity and allergy.
In this project, the student will contribute to the analysis of the impact of colostrum on obesity susceptibility in adulthood. Therefore, animal model will be used to analyze impact of colostrum on adipose tissue expansion, energy expenditure and insulin sensitivity. In parallel, studies in human birth cohort will be analyzed for translation of data obtained in mice.